Identification and pharmacome analysis of receptor phenotypes originated from a single gene

每一种蛋白质，如受体或酶，都是根据一个相应的基因进行生物合成的。然而，蛋白质在表达后，可能会经常被天然细胞和组织中的多种因素修饰，从而使这些蛋白质不再表现出单一的性质。我们建议将存在于天然组织中的所有这类蛋白质命名为“药物组”。在本研究中，我们对α1-肾上腺素能受体(AR)进行了药物组学分析。首先，我们在下尿路中发现了一种独特的A1-AR介导的肾上腺素能收缩，由于其对哌唑嗪的亲和力较低而被命名为A1 L-AR。A1 L-AR通过与完整组织切片结合的方法鉴定，但不与膜制剂结合。因此，AFT-AR在均质时向上转换为A1A-AR，表明这两个A1-AR之间可能存在关系。然后我们检测了A1-Ars的基因敲除(KO)效应。在野生型、A1B-KO和A1D-KO小鼠中，A1 L-AR在功能和结合研究中被鉴定。然而，在A1 A-K0小鼠中，不仅A1A-AR而且A1L-AR被取消。这些结果表明，A1a-AR和1L-ARs都来源于A1a-AR基因，表明不同的表型是由一个基因表达的。

Every protein such as a receptor or enzyme is biosynthesized according to one corresponding gene. However, after expression, proteins may be frequently modified by many factors innative cells and tissues, so that these proteins no longer exhibit a single property. We have proposed t hat all of such proteins occurring in native tissues are designated as the `pharmacome'. In this study, we performed pharmacome analysis of α1-adrenoceptor (AR). At first, we found a unique a1-AR mediating adrenergic contraction in lower urinary tract and named as a1 L-AR because of its low affinity for prazosin. The a1 L-AR was identified by binding approach with intact tissue segments but not with membrane preparations. Thus, aft-AR converted to a1A-AR up on homogenization, suggesting a possible relationship between the both a1-ARs. Then we examined the effects of knockout (KO) of a1 -ARs. In wild-type, a1B-KO and a1D-KO mice, a1 L-AR was identified in functional and binding studies. However, in a1 A-K0 mice, not only a1A-AR but also a1L-AR was abolished. From these results it is concluded that both a1A-and a 1L-ARs are derived from a1A-AR gene, indicating that different phenotypes are expressed from a single gene.